ma-1 and Neoplasm-Metastasis

Regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) have have been shown to improve overall survival in patients with refractory metastatic colorectal cancer. The aim of our study was to evaluate the efficacy and safety profiles of these agents administered in sequence in real world practice.. Clinical data of patients treated beyond the 2°line with REG or FTD/TPI between January 2016 and August 2020, were retrospectively collected from eight institutes in the Lazio Region.. We included 49 patients treated with both drug sequences. A total of 28 G3/G4 toxicity events (53.8%) were recorded in the FTD/TPI-to-REG sequence vs. 24 (46.1%) in the reverse sequence. Median overall survival for the patients included in the FTP/TPI-to-REG group was 20 months (95%CI=16.7-23.3) vs. 27 months in the reverse group (95%CI=17.8-36.2). The disease control rate was 45.0% for patients treated with the REG-to-FTD/TPI sequence vs. 24.1% in those treated with the FTD/TPI-to-REG sequence (p=0.18).. The sequence REG-to-FTD/TPI and vice versa can extend survival, whereas only REG-to-FTD/TPI stabilizes cancer growth.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Phenylurea Compounds; Progression-Free Survival; Pyridines; Pyrrolidines; Thymine; Trifluridine

Trifluridine and tipiracil (FTD + TPI) and regorafenib (REG) are approved treatments for the treatment of refractory metastatic colorectal cancer (mCRC). This study assesses adherence and duration of therapy with FTD + TPI versus REG and explores the effect of sequencing on adherence.. Adults diagnosed with mCRC were identified in the IQVIA Real-World Data Adjudicated Claims: U.S. database (October 2014-July 2017). The observation period spanned from the index date (first dispensing of FTD + TPI or REG) to the earliest of a switch to another mCRC agent, the end of continuous enrollment, or the end of data availability. Medication possession ratio (MPR), proportion of days covered (PDC), and persistence and time to discontinuation (gap ≥45 days) were compared between FTD + TPI and REG users and among switchers (FTD + TPI-to-REG vs. REG-to-FTD + TPI).. A total of 469 FTD + TPI and 311 REG users were identified. FTD + TPI users had higher compliance with an MPR ≥80% (odds ratio [OR], 2.47; p < .001) and PDC ≥80% (OR, 2.77; p < .001). FTD + TPI users had better persistence (82.8% vs. 68.0%; p < .001) and lower risk of discontinuation (hazard ratio [HR], 0.76; p = .006). Among switchers (96 FTD + TPI-to-REG; 83 REG-to-FTD + TPI), those switching from FTD + TPI to REG were more likely to have an MPR ≥80% (OR, 2.91; p < .001) and PDC ≥80% (OR, 4.60; p < .001) compared with REG-to-FTD + TPI switchers while treated with these drugs. Additionally, FTD + TPI-to-REG switchers had a lower risk of first treatment discontinuation (HR, 0.66; p = .009).. FTD + TPI users had significantly higher adherence and persistence, and patients who were treated with FTD + TPI before switching to REG also had higher adherence and persistence outcomes.. Trifluridine plus tipiracil (FTD + TPI) and regorafenib (REG) prolong survival in refractory metastatic colorectal cancer (mCRC) but have different tolerability profiles. This study assessed real-world adherence to treatment with FTD + TPI versus REG and compared outcomes among patients who switched from FTD + TPI to REG and vice versa. FTD + TPI was associated with significantly higher medication adherence and longer time to discontinuation than REG. Patients treated with FTD + TPI prior to switching to REG also showed higher adherence outcomes. Findings could help inform decision making regarding the choice and sequencing of treatment with FTD + TPI versus REG in patients with mCRC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Colorectal Neoplasms; Drug Combinations; Female; Humans; Longitudinal Studies; Male; Medication Adherence; Middle Aged; Neoplasm Metastasis; Phenylurea Compounds; Pyridines; Pyrrolidines; Retrospective Studies; Thymine; Trifluridine

Topics: Drug Combinations; Drug Costs; Humans; Neoplasm Metastasis; Pyrrolidines; Stomach Neoplasms; Thymine; Trifluridine

Trifluridine/tipiracil has been approved for the treatment of refractory metastatic colorectal cancer. Adverse effects of this drug combination include leukopenia, neutropenia, fatigue, diarrhea, and vomiting. We present a case of trifluridine/tipiracil-induced leukocytoclastic vasculitis (LCV) with late-onset Henoch-Schönlein purpura (HSP) in a 42-year-old man with metastatic appendiceal cancer. The patient's biopsy-proven LCV developed one month after he began trifluridine/tipiracil treatment and resolved after discontinuation of the drug. He presented to the emergency department two months after the appearance of his LCV with shortness of breath, elevated blood pressure, elevated creatinine, hematuria, and proteinuria. A kidney biopsy was performed and the presence of IgA deposits and cellular crescents indicated rapidly progressive glomerulonephritis secondary to Henoch-Schönlein purpura (HSP). Neither LCV nor HSP have been reported as adverse effects of trifluridine/tipiracil treatment. Malignancy as a cause of our patient's HSP is another possibility. The delay between our patient's skin findings and acute renal failure indicates that suspected HSP should be monitored by urinalysis for a period of time owing to the risk of life-threatening renal disease.

Topics: Adult; Appendiceal Neoplasms; Fatal Outcome; Glomerulonephritis; Humans; IgA Vasculitis; Kidney Failure, Chronic; Male; Neoplasm Metastasis; Pyrrolidines; Thymine; Trifluridine; Vasculitis, Leukocytoclastic, Cutaneous

Professor Alfredo Falcone and Dr Lisa Salvatore speak to Roshaine Gunawardana, Managing Commissioning Editor: Professor Alfredo Falcone is the Director of the Department of Oncology and the Specialization School at the University Hospital of Pisa, Italy. He trained in Pisa and Genoa, Italy, and has held major positions in Italian oncology since 2000. He currently has more than 300 publications, including papers in peer-reviewed international and national journals, book chapters, and more than 600 abstracts of presentations to international and national conferences. The majority of his papers regard clinical and translational research, with a particular focus on metastatic colorectal cancer. Dr Lisa Salvatore is a medical oncologist in the Department of Translational Research and New Technologies in Medicine and Surgery at the University of Pisa. She has been an author on about 40 publications in major peer-reviewed publications and has made numerous presentations in national and international conferences. Her main interest is focused on clinical and translational research in metastatic colorectal cancer.

Topics: Achievement; Antineoplastic Combined Chemotherapy Protocols; Career Choice; Clinical Trials as Topic; Colorectal Neoplasms; Disease Management; Drug Discovery; Humans; Neoplasm Metastasis; Neoplasm Staging; Pyrrolidines; Research; Thymine; Treatment Outcome; Trifluridine